Prostate cancer is one of the most common cancers in U.S. men. Serum prostate specific antigen (PSA) test, a biomarker of prostate cancer, and the digital rectal examination (DRE) have been used for prostate cancer screening. Men with elevated serum PSA levels, serum PSA velocity of >= 0.35 ng/mL per year, or abnormal DRE have been believed to be at higher risk for prostate cancer. However, serum PSA test has a low specificity and the DRE has a low sensitivity. As a result, some false positives are discovered at prostate biopsy, resulting in an unnecessary biopsy that can cause complications such as prostate and urinary infections as well as emotional stress. Therefore, more specific biomarkers for prostate cancer are needed to make a more accurate diagnosis. MicroRNAs (miRNAs), non-coding RNAs, may be potential biomarkers for prostate cancer. MicroRNAs have been shown to be deregulated in cancers; and, few studies have found significant differences in miRNAs expression levels between benign and malignant prostatic tissues and between men with and without prostate cancer in serum specimen. However, the relationship between miRNAs and prostate cancer remains unclear due to inconsistent study findings; and, the relationship between miRNAs and possible precancerous prostatic lesions (atypia and high-grade prostate intraepithelial neoplasia) have not been examined. In this application, we propose to examine whether specific miRNAs could be potential biomarkers for prostate cancer by examining miRNAs expression levels among men who had a positive prostate cancer screening test. In addition, we propose to examine whether specific miRNAs could be used to monitor prostate disease status of men being treated for prostate cancer. We propose to investigate the following specific aims: 1) to examine whether there are >= 2-fold mean differences in expression levels of 377 miRNAs in plasma specimen of men with biopsied-confirmed no prostate cancer (n=65) versus biopsied-confirmed precancerous prostatic lesions (n=65) versus biopsied-confirmed, localized prostate cancer (n=65), and 2) to examine whether there are significant decreases in expression levels of 20 miRNAs (ones that are elevated in prostate cancer men that have the greatest mean fold difference to no prostate cancer men in Aim 1) in plasma specimen at pre- to 3-month post-radical prostatectomy in a cohort of biopsied-confirmed, localized prostate cancer men (n=50). This proposed research study has the potential to influence public health policy by providing information on which individuals need to be screened or treated for prostate cancer, which ultimately will reduce prostate-related morbidity and prostate cancer mortality.